Mechanical forces play an important role in embryonic morphogenesis. In Caenorhabditis elegans, muscle contractions in the early embryo drive axial elongation, but it has remained unclear how these mechanical signals are coordinated on the scale of the whole embryo. In a new study, Llense and colleagues used calcium imaging and RNA interference to understand how these contractions are initiated, and to identify key molecular players. We spoke to first author Flora Llense and corresponding author Michel Labouesse, Professor at Sorbonne Université, Paris, France, to find out more.
The Labouesse lab, with Michel Labouesse in the centre, holding a multichannel pipette, and Flora Llense in front of him, holding a rack of plates.
Michel, what questions are your lab trying to answer?
ML: For this paper, the general issue we focused on was how different tissues coordinate their morphogenesis through mechanical input, and how a given mechanical force then regulates subcellular processes (be it cytoskeleton remodelling, junction remodelling, trafficking, polarity, etc.). The more-specific question we looked at here was: how are C. elegans muscle contractions initiated and coordinated?
Flora, how did you come to work in the lab and what drives your research today?
FL: I first met Michel during my PhD while participating in a European consortium in the Escorial near Madrid. Later, in 2014, during my postdoctoral research, I attended a seminar at the Pasteur Institute where Michel presented his work on how cell shape is maintained during morphogenesis – a topic I found absolutely fascinating. Around that time, an assistant professor position opened in his lab. I applied and was fortunate to be selected for the permanent position.
Can you tell us about the background of the field that inspired your work?
ML: An early inspiring article was by the late Lewis Wolpert, who wrote an opinion piece written for Science in 1994 entitled ‘Do we understand development?’ (Wolpert, 1994), in which he was arguing that we don't understand morphogenesis and the role of mechanical forces. That paper made me embrace the study of morphogenesis and mechanical forces. Another paper was the description of the effects of uniaxial stretch on cells (Katsumi et al., 2002), which made me think that perhaps muscle contractions might similarly influence epidermal cells. We eventually established it was the case, and the present study is one aspect of this early influence.
FL: I was first introduced to the concept of mechanotransduction and the pioneering work of Michael Sheetz during my initial studies. His research provided valuable insights into the mechanisms by which cells detect and respond to mechanical stimuli, significantly enriching my understanding of cellular processes.
Can you give us the key results of the paper?
ML & FL: The most unexpected finding was the identification of inx-15, which is known to act in the intestine. The key result was the identification of sets of cells acting as leader cells, which implied a specific mechanism for coordination with non-leader muscles.
I feel that we have come to a decent understanding of the influence of muscle contractions in C. elegans morphogenesis
A C. elegans embryo showing a reporter construct for inx-15 in red and membrane-labelled muscle in green.
A C. elegans embryo showing a reporter construct for inx-15 in red and membrane-labelled muscle in green.
When doing the research, did you have any particular result or eureka moment that has stuck with you?
ML & FL: The first time we observed that photoablation of the two potential leader cells impaired muscle contractions, embryo twitching and overall embryonic elongation was a moment of pure joy.
Why did you choose to submit this paper to Development?
Because we felt that it was meant for Development as it describes a fundamental developmental process.
Flora, what is next for you after this paper?
FL: I am currently working in François Robin's laboratory, where we focus on understanding how the composition of the actomyosin cytoskeleton varies during morphogenesis and impacts the mechanical properties of the actin cortex.
Michel, where will this story take your lab next?
ML: Retirement – this will be my last paper along with another about to be accepted. I'm very proud of both as I feel that we have come to a decent understanding of the influence of muscle contractions in C. elegans morphogenesis.
Finally, let's move outside the lab – what do you like to do in your spare time?
ML: I enjoy painting, gardening and learning foreign languages (currently Italian).
FL: I love hiking in the French Pyrenees and enjoy being surrounded by nature, breathing in the fresh air and taking long walks with my family.
Laboratoire Développement, Adaptation et Vieillissement, Sorbonne Université, IBPS, Dev2A, CNRS UMR8263 – Inserm U1345, 7 Quai St-Bernard, 75005 Paris, France.
E-mail: [email protected]; [email protected]
